The present invention relates to a method of mass spectrometry and a mass spectrometer. The preferred embodiment relates to digitising a plurality of individual signals or transients using an Analogue to Digital Converter (“ADC”) and summing the digitised signals or transients or time and intensity values relating to the digitised signals or transients to generate a composite mass spectrum.
It is known to record or digitise individual signals or transients arising from ion arrivals at an ion detector or electron multiplier using an Analogue to Digital recorder or an Analogue to Digital Converter (“ADC”). Orthogonal acceleration Time of Flight mass spectrometers may digitise ion arrival signals or transients relating to many thousands of individual time of flight separations. The digitised signals or transients are summed to produce a final summed or composite time of flight mass spectrum.
Each individual time of flight spectrum, signal or transient may be processed in real time before summing. In the simplest case this processing may be the application of an amplitude threshold to isolate signal arising from ion arrivals from background noise or baseline noise. The signal at individual digitised samples (i.e. individual ADC time bins) or within a time of flight spectrum which is above the threshold is recorded and all other samples or intensity values in ADC time bins are set to zero or to a baseline value. Such a method is disclosed, for example, in US 2011/0049353 (Micromass).
Multiple time of flight spectra processed in this way may then be summed or averaged to generate a final summed spectrum with reduced noise.
It is also known to process individual signals or transients which have been digitised to reduce the ion arrival signals or transients into time and intensity pairs. Such a method is disclosed, for example, in U.S. Pat. No. 8,063,358 (Micromass).
Individual signals or transients which are reduced to time and intensity pairs may then be summed with other time and intensity pairs relating to other time of flight spectra, signals or transients in order to produce a final summed, composite or average spectrum. This method advantageously substantially removes the profile or line width of the digitised signal from the final summed spectra thereby increasing the effective time of flight resolution.
It is known that at high ion arrival rates the intensity of one or more digitisation samples (i.e. the signal intensity during an ADC time bin) may exceed the dynamic range of the ADC. As a result, the intensity value will be saturated. This saturation leads to errors in the final intensity and/or temporal position of the summed spectrum.
State of the art electron multipliers or photo multipliers produce signals of statistically varying intensity for identical numbers of arriving ions of the same charge state and mass to charge value. The intensity probability distribution is known as the pulse height distribution (“PHD”) of the ion detector. For many Time of Flight ion detectors the PHD may be approximated by a Gaussian distribution with a mean approximately the same as the FWHM.
It is common that a spectral peak resulting from summing multiple digitised signals can contain a proportion of signals wherein the ion arrival intensity saturated the ADC and hence the recorded intensity values in some of the ADC time bins is saturated.
The response of the ion detector is mass to charge ratio and charge state dependent due to differences in electron yield related to the velocity and energy of primary ion strikes. If the charge state is not known then the average ion arrival rate cannot be estimated.
A further complication is that an instrument parameter may be stepped, scanned or otherwise varied during the summation time of the individual time of flight spectra. For example, the collision energy or RF amplitude of an ion-optical component may be varied during the summation period to optimize conditions across a wide mass to charge ratio range. In this case the ion arrival rate may change during summation. However, the ion arrival rate cannot be easily estimated for any particular mass to charge ratio value.
Ions may also be delivered to a Time of Flight mass analyser at different ion arrival rates during the summation due to other effects such as pre-separation by ion mobility or by virtue of using a Matrix Assisted Laser Desorption Ionisation (“MALDI”) or other pulsed ion source.
In addition, many sample introduction techniques produce ion currents which vary rapidly with time including chromatographic, distillation and vaporization introduction techniques.
US 2011/0226943 (Räther) discloses a method of correcting an individual ion signal or transient which suffers from saturation. According to an arrangement a field programmable gate array (“FPGA”) counts the measured values of an individual digitised ion signal or single digitised transient which are in saturation. An arithmetic unit then adds a corrected measurement value from a table to the sum spectra at the position of the time of flight that corresponds to the centre of the saturation range.
WO 2012/095647 (Micromass) discloses a method of processing multidimensional mass spectrometry data, wherein the multidimensional data may comprise liquid chromatography retention time and time of flight data. Regions of interest are identified within the raw multidimensional data and peak detection is used to account for mass and/or intensity errors in the raw data arising from hardware limitations (e.g. TDC deadtime) so as to produce an improved data set.
GB-2417125 (Micromass) discloses an ion beam attenuator wherein the degree of attenuation may be varied by varying a mark space ratio of the attenuator. The attenuator may be switched between two modes of operation and mass spectral data may be obtained in both modes of operation (e.g. 100% transmission and 2% transmission). The mass spectral data in the 100% transmission mode may be interrogated and any mass peaks which are suffering from saturation may be flagged. A final composite mass spectrum may be obtained using a combination of both high transmission mass spectral data and low transmission mass spectral (where the corresponding high transmission mass spectral data suffers from saturation).
WO 2012/080443 (Makarov) discloses a data acquisition system comprising two detectors for outputting two detection signals in separate channels in response to ions arriving at the detection system. Two aligned signals in separate channels CH1 and CH2 are input to a merge module, wherein a merged (HDR) spectrum is generated. The module uses a high gain channel CH2 to provide the peaks for the merged HDR spectrum except where the high gain detection signal is saturated (e.g. as detected from the presence of an overflow flag associated with the peak in the high gain detection signal). Where saturation of a peak occurs in the high gain channel CH2, the corresponding peak from the low gain channel CH1 and signal is instead used for the merged HDR spectrum.
GB-2457112 (Micromass) discloses a method of detecting ions wherein an ion detector is arranged simultaneously to output first and second signals. The two signals are digitised and ion peaks having an intensity corresponding with a full scale digitised output are flagged. If ion peaks in the second signal are flagged as suffering from saturation then corresponding mass spectral data from the first signal is utilised.
It is desired to provide an improved mass spectrometer and method of mass spectrometry.